Natural cell mediated immunity is frequently decreased in individuals who meet the case definition of chronic fatigue syndrome (CFS). Our research group and others have noted that exposures of healthy individuals as well as immunocompromised persons to acute and chronic stressors have an adverse effect on natural killer (NK) cell function, and that this adverse stress effect is susceptible to amelioration by behavioral interventions in which cognitive restructuring and relaxation training are taught. In this Multidisciplinary Research Center, Project 2 will carry out such an intervention for individuals who meet the diagnosis criteria for CFS. The intervention will be carried out over a 12 week period. Blood samples from both pre-intervention and post-intervention will be available for study in Project 4. Also available will be 2 samples collected 12 weeks apart on CFS subjects who do not receive the intervention, but are in an education/control condition. The Administrative Core will enroll healthy, sedentary controls for both Project l and Project 4 and for the Laboratory Core as normal subjects for all assays being done. The proposed Center will provide a mechanism to advance our understanding of NK cells and CFS. A detailed comparison will be made of markers of NK cell cytotoxic capacity as well as actual killing of tumor cell target cells. The differences between effect of the intervention on NK cell function can be evaluated. In addition to the traditional chromium release cytotoxicity assay, Project 4 will look at important markers of NK cell functional status not yet evaluated in CFS. These will include flow cytometric determination of intracellular perforin and determination of degree of expression on NK cells of the surface membrane adhesion molecules, L-selectin (CD62L), LFA-1 (CDlla) and CD56 by fluorescence intensity measurements. These substances are associated with the ability of NK cells to-kill target cells and/or to interact with vascular epithelial cells and pass from peripheral circulation into tissue. The relationship of these markers to the low NK cell activity associated with CFS, to effects of acute and chronic stress on NK cell function or to the modulation of life stress by behavioral interventions has not previously been studied. We will examine the effects on NK cell cytotoxicity, intracellular perforin levels and surface markers of in vitro exposure of peripheral blood cells to stress hormones (epinephrine, norepinephrine, cortisol) and tumor necrosis factor-o:. All of these studies will be done pre/post intervention in the 2 CFS groups of subjects and one time in the healthy, sedentary controls. This design will allow the determination of differences between CFS and healthy controls as well as the impact of the behavioral intervention by comparing findings before and following the intervention relative to CFS control subjects.